The present invention relates to polycarbonates for delivery of drugs and methods of preparation thereof, and more specifically to block copolymers comprising polycarbonates bearing pendant steroidal groups for delivery of hydrophobic anticancer drugs.
One of the major problems in the development of anticancer drug formulations is the delivery of the drugs with adequately high bioavailability for therapeutic intention. As many anticancer agents are hydrophobic, clinical administration of these drugs typically requires dissolution using organic solvents. One such agent is paclitaxel, which is a widely used small molecular drug effective against an extensive range of solid tumors. However, its clinical applications have been mostly impeded by its extremely low aqueous solubility (0.3 micrograms/mL in water), which limits its administration to the use of a formulation comprising of 50:50 mixture of Cremophor EL (polyethoxylated castor oil):ethanol. Although this formulation is able to increase the solubility and bioavailability of paclitaxel (PTX), it can also lead to hypersensitivity reactions and other severe side effects in some cases. Despite premedication with corticosteroids to reduce the immune response, minor reactions such as rashes and flushing still occur in 41% to 44% of patients and potentially fatal reactions occur in 1.5% to 3% of patients.
Additional materials and methods are needed for administering hydrophobic drugs.